tbuckley/cabot-search huggingface dataset:
Association of a Housing Mobility Program With Childhood Asthma Symptoms and Exacerbations
Authors: Craig Evan Pollack, Laken C. Roberts, Roger D. Peng, Pete Cimbolic, David Judy, Susan Balcer-Whaley, Torie Grant, Ana Rule, Stefanie Deluca, Meghan F. Davis, Rosalind J. Wright, Corinne A. Keet, Elizabeth C. Matsui
Journal: JAMA (2023)

Importance Structural racism has been implicated in the disproportionally high asthma morbidity experienced by children living in disadvantaged, urban neighborhoods. Current approaches designed to reduce asthma triggers have modest impact. Objective To examine whether participation in a housing mobility program that provided housing vouchers and assistance moving to low-poverty neighborhoods was associated with reduced asthma morbidity among children and to explore potential mediating factors. Design, Setting, and Participants Cohort study of 123 children aged 5 to 17 years with persistent asthma whose families participated in the Baltimore Regional Housing Partnership housing mobility program from 2016 to 2020. Children were matched to 115 children enrolled in the Urban Environment and Childhood Asthma (URECA) birth cohort using propensity scores. Exposure Moving to a low-poverty neighborhood. Main Outcomes Caregiver-reported asthma exacerbations and symptoms. Results Among 123 children enrolled in the program, median age was 8.4 years, 58 (47.2%) were female, and 120 (97.6%) were Black. Prior to moving, 89 of 110 children (81%) lived in a high-poverty census tract (&amp;amp;gt;20% of families below the poverty line); after moving, only 1 of 106 children with after-move data (0.9%) lived in a high-poverty tract. Among this cohort, 15.1% (SD, 35.8) had at least 1 exacerbation per 3-month period prior to moving vs 8.5% (SD, 28.0) after moving, an adjusted difference of −6.8 percentage points (95% CI, −11.9% to −1.7%; P = .009). Maximum symptom days in the past 2 weeks were 5.1 (SD, 5.0) before moving and 2.7 (SD, 3.8) after moving, an adjusted difference of −2.37 days (95% CI, −3.14 to −1.59; P &amp;amp;lt; .001). Results remained significant in propensity score–matched analyses with URECA data. Measures of stress, including social cohesion, neighborhood safety, and urban stress, all improved with moving and were estimated to mediate between 29% and 35% of the association between moving and asthma exacerbations. Conclusions and Relevance Children with asthma whose families participated in a program that helped them move into low-poverty neighborhoods experienced significant improvements in asthma symptom days and exacerbations. This study adds to the limited evidence suggesting that programs to counter housing discrimination can reduce childhood asthma morbidity.
Uncertainties in the Analysis of Heart Rate Variability: A Systematic Review
Authors: Lei Lu, Tingting Zhu, Davide Morelli, Andrew Creagh, Zhangdaihong Liu, Jenny Yang, Fenglin Liu, Yuan-Ting Zhang, David A. Clifton
Journal: IEEE Reviews in Biomedical Engineering (2023)

Heart rate variability (HRV) is an important metric with a variety of applications in clinical situations such as cardiovascular diseases, diabetes mellitus, and mental health. HRV data can be potentially obtained from electrocardiography and photoplethysmography signals, then computational techniques such as signal filtering and data segmentation are used to process the sampled data for calculating HRV measures. However, uncertainties arising from data acquisition, computational models, and physiological factors can lead to degraded signal quality and affect HRV analysis. Therefore, it is crucial to address these uncertainties and develop advanced models for HRV analysis. Although several reviews of HRV analysis exist, they primarily focus on clinical applications, trends in HRV methods, or specific aspects of uncertainties such as measurement noise. This paper provides a comprehensive review of uncertainties in HRV analysis, quantifies their impacts, and outlines potential solutions. To the best of our knowledge, this is the first study that presents a holistic review of uncertainties in HRV methods and quantifies their impacts on HRV measures from an engineer's perspective. This review is essential for developing robust and reliable models, and could serve as a valuable future reference in the field, particularly for dealing with uncertainties in HRV analysis.
Racial Differences in Quality of Life in Patients With Heart Failure Treated With Sodium–Glucose Cotransporter 2 Inhibitors: A Patient-Level Meta-Analysis of the CHIEF-HF, DEFINE-HF, and PRESERVED-HF Trials
Authors: Kashvi Gupta, John A. Spertus, Mary Birmingham, Kensey L. Gosch, Mansoor Husain, Dalane W. Kitzman, Bertram Pitt, Sanjiv J. Shah, James L. Januzzi, Ildiko Lingvay, Javed Butler, Mikhail Kosiborod, David E. Lanfear
Journal: Circulation (2023)

Health status outcomes, including symptoms, function, and quality of life, are worse for Black compared with White patients with heart failure. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular mortality and improve health status in patients with heart failure, but whether the health status benefit of SGLT2is is similar across races is not established. The objective of this study was to compare the treatment effect of SGLT2is (versus placebo) on health status for Black compared with White patients with heart failure.
Sex‐specific analysis of the rapid up‐titration of guideline‐directed medical therapies after a hospitalization for acute heart failure: Insights from the <scp>STRONG‐HF</scp> trial
Authors: Kamilė Čerlinskaitė‐Bajorė, Carolyn S.P. Lam, Karen Sliwa, Marianna Adamo, Jozine M. Ter Maaten, Valentine Léopold, Alexandre Mebazaa, Beth Davison, Christopher Edwards, Mattia Arrigo, Marianela Barros, Jan Biegus, Ovidiu Chioncel, Alain Cohen‐Solal, Albertino Damasceno, Rafael Diaz, Gerasimos Filippatos, Etienne Gayat, Antoine Kimmoun, Marco Metra, Maria Novosadova, Matteo Pagnesi, Peter S. Pang, Piotr Ponikowski, Hadiza Saidu, Koji Takagi, Daniela Tomasoni, Adriaan A. Voors, Gad Cotter, Jelena Čelutkienė
Journal: European Journal of Heart Failure (2023)

The aim of this study was to evaluate efficacy and safety of rapid up-titration of guideline-directed medical therapies (GDMT) in men and women hospitalized for acute heart failure (AHF).In STRONG-HF, AHF patients were randomized just prior to discharge to either usual care (UC) or a high-intensity care (HIC) strategy of GDMT up-titration. In these analyses, we compared the implementation, efficacy, and safety of the HIC strategy between men and women. In the randomized AHF population, 416/1078 (39%) were women. By day 90, a higher proportion of both sexes in the HIC group had been up-titrated to full doses of GDMT compared to UC. Overall, there were no differences in the primary endpoint between the sexes. The primary endpoint, 180-day heart failure readmission or death, occurred in 15.8% HIC women versus 23.5% women in the UC group (adjusted hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.40-1.13) and in 14.9% HIC men versus 23.5% UC men (adjusted HR 0.57, 95% CI 0.38-0.88) (adjusted interaction p = 0.65). There was no significant treatment-by-sex interaction in quality-of-life improvement or in adverse events, including serious or fatal adverse events.The results of the current analyses suggest that a rapid up-titration of GDMT immediately after an AHF hospitalization can and should be implemented similarly in men and women, as it results in reduction of 180-day all-cause death or heart failure readmission, quality-of-life improvement in both men and women with a similar safety profile.
Etiological cure prevents further decompensation and mortality in patients with cirrhosis with ascites as the single first decompensating event
Authors: Marta Tonon, Lorenz Balcar, Georg Semmler, Valeria Calvino, Bernhard Scheiner, Simone Incicco, Anna Barone, Rafael Paternostro, Carmine G. Gambino, David Josef M. Bauer, Antonio Accetta, Lukas Hartl, Alessandra Brocca, Mathias Jachs, Michael Trauner, Mattias Mandorfer, Paolo Angeli, Thomas Reiberger, Salvatore Piano
Journal: Hepatology (2023)

Background and Aims: Removal/suppression of the primary etiological factor reduces the risk of decompensation and mortality in compensated cirrhosis. However, in decompensated cirrhosis, the impact of etiologic treatment is less predictable. We aimed to evaluate the impact of etiological treatment in patients with cirrhosis who developed ascites as single index decompensating event. Approach and Results: Patients with cirrhosis and ascites as single first decompensation event were included and followed until death, liver transplantation, or Q3/2021. The etiology was considered “cured” (alcohol abstinence, hepatitis C cure, and hepatitis B suppression) versus “controlled” (partial removal of etiologic factors) versus “uncontrolled.” A total of 622 patients were included in the study. Etiology was “cured” in 146 patients (24%), “controlled” in 170 (27%), and “uncontrolled” in 306 (49%). During follow-up, 350 patients (56%) developed further decompensation. In multivariable analysis (adjusted for age, sex, varices, etiology, Child-Pugh class, creatinine, sodium, and era of decompensation), etiological cure was independently associated with a lower risk of further decompensation (HR: 0.46; p = 0.001). During follow-up, 250 patients (40.2%) died, while 104 (16.7%) underwent LT. In multivariable analysis, etiological cure was independently associated with a lower mortality risk (HR: 0.35, p &lt; 0.001). Conclusions: In patients with cirrhosis and ascites as single first decompensating event, the cure of liver disease etiology represents a main treatment goal since this translates into considerably lower risks of further decompensation and mortality.
Midbrain dopamine oxidation links ubiquitination of glutathione peroxidase 4 to ferroptosis of dopaminergic neurons
Authors: Jie Sun, Xiao-Min Lin, Dan-Hua Lu, Meng Wang, Kun Li, Sheng-Rong Li, Zheng-Qiu Li, Cheng-Jun Zhu, Zhi-Min Zhang, Chang-Yu Yan, Ming-Hai Pan, Hai-Biao Gong, Jing-Cheng Feng, Yun-Feng Cao, Feng Huang, Wan-Yang Sun, Hiroshi Kurihara, Yi-Fang Li, Wen-Jun Duan, Gen-Long Jiao, Li Zhang, Rong-Rong He
Journal: Journal of Clinical Investigation (2023)

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the gradual loss of midbrain dopaminergic neurons in association with aggregation of α-synuclein. Oxidative damage has been widely implicated in this disease, though the mechanisms involved remain elusive. Here, we demonstrated that preferential accumulation of peroxidized phospholipids and loss of the antioxidant enzyme glutathione peroxidase 4 (GPX4) were responsible for vulnerability of midbrain dopaminergic neurons and progressive motor dysfunctions in a mouse model of PD. We also established a mechanism wherein iron-induced dopamine oxidation modified GPX4, thereby rendering it amenable to degradation via the ubiquitin-proteasome pathway. In conclusion, this study unraveled what we believe to be a novel pathway for dopaminergic neuron degeneration during PD pathogenesis, driven by dopamine-induced loss of antioxidant GPX4 activity.
Mechanistic advances in osteoporosis and anti‐osteoporosis therapies
Authors: Haiwei Wang, Yuchuan Luo, Haisheng Wang, Feifei Li, Fanyuan Yu, Ling Ye
Journal: MedComm (2023)

Osteoporosis is a type of bone loss disease characterized by a reduction in bone mass and microarchitectural deterioration of bone tissue. With the intensification of global aging, this disease is now regarded as one of the major public health problems that often leads to unbearable pain, risk of bone fractures, and even death, causing an enormous burden at both the human and socioeconomic layers. Classic anti-osteoporosis pharmacological options include anti-resorptive and anabolic agents, whose ability to improve bone mineral density and resist bone fracture is being gradually confirmed. However, long-term or high-frequency use of these drugs may bring some side effects and adverse reactions. Therefore, an increasing number of studies are devoted to finding new pathogenesis or potential therapeutic targets of osteoporosis, and it is of great importance to comprehensively recognize osteoporosis and develop viable and efficient therapeutic approaches. In this study, we systematically reviewed literatures and clinical evidences to both mechanistically and clinically demonstrate the state-of-art advances in osteoporosis. This work will endow readers with the mechanistical advances and clinical knowledge of osteoporosis and furthermore present the most updated anti-osteoporosis therapies.
Genetic predisposition to neuroblastoma results from a regulatory polymorphism that promotes the adrenergic cell state
Authors: Nina Weichert-Leahey, Hui Shi, Ting Tao, Derek A. Oldridge, Adam D. Durbin, Brian J. Abraham, Mark W. Zimmerman, Shizhen Zhu, Andrew C. Wood, Deepak Reyon, J. Keith Joung, Richard A. Young, Sharon J. Diskin, John M. Maris, A. Thomas Look
Journal: Journal of Clinical Investigation (2023)

Childhood neuroblastomas exhibit plasticity between an undifferentiated neural crest-like mesenchymal cell state and a more differentiated sympathetic adrenergic cell state. These cell states are governed by autoregulatory transcriptional loops called core regulatory circuitries (CRCs), which drive the early development of sympathetic neuronal progenitors from migratory neural crest cells during embryogenesis. The adrenergic cell identity of neuroblastoma requires LMO1 as a transcriptional cofactor. Both LMO1 expression levels and the risk of developing neuroblastoma in children are associated with a single nucleotide polymorphism, G/T, that affects a GATA motif in the first intron of LMO1. Here, we showed that WT zebrafish with the GATA genotype developed adrenergic neuroblastoma, while knock-in of the protective TATA allele at this locus reduced the penetrance of MYCN-driven tumors, which were restricted to the mesenchymal cell state. Whole genome sequencing of childhood neuroblastomas demonstrated that TATA/TATA tumors also exhibited a mesenchymal cell state and were low risk at diagnosis. Thus, conversion of the regulatory GATA to a TATA allele in the first intron of LMO1 reduced the neuroblastoma-initiation rate by preventing formation of the adrenergic cell state. This mechanism was conserved over 400 million years of evolution, separating zebrafish and humans.
Characterization of <i>Bifidobacterium kashiwanohense</i> that utilizes both milk- and plant-derived oligosaccharides
Authors: Kento Orihara, Kana Yahagi, Yuki Saito, Yohei Watanabe, Toshio Sasai, Taeko Hara, Naoki Tsukuda, Kaihei Oki, Junji Fujimoto, Takahiro Matsuki
Journal: Gut Microbes (2023)

Bifidobacteria are prominent members of the human gut microbiota throughout life. The ability to utilize milk- and plant-derived carbohydrates is important for bifidobacterial colonization of the infant and adult gut. The
Torsemide vs Furosemide After Discharge and All-Cause Mortality in Patients With Heart Failure
Authors: William R. Wolowich
Journal: JAMA (2023)

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Is end-of-life anticipatory prescribing always enough?
Authors: Ben Bowers, Paul Howard, Bella Madden, Kristian Pollock, Stephen Barclay
Journal: BMJ (2023)

End-of-life anticipatory prescribing can give patients timely access to symptom relieving drugs in their last days and hours, but improved review, provision, and personalisation of medication is needed, write <b>Ben Bowers and colleagues</b>
US Physicians’ Self-reported Discussions About Tobacco-Free Nicotine Pouches During Clinical Encounters With Patients in 2021
Authors: Mary Hrywna, Michelle T. Bover-Manderski, Olivia A. Wackowski, Michael B. Steinberg, Cristine D. Delnevo
Journal: JAMA Network Open (2023)

This survey study assesses the extent to which physicians discussed tobacco-free nicotine pouches during clinical encounters with patients.
Association of 5α-Reductase Inhibitor Prescription With Bladder Cancer Progression in Males in South Korea
Authors: Min Ho An, Min Seo Kim, Chungsoo Kim, Tae Il Noh, Kwan Joong Joo, Dong Hun Lee, Kyu-Ho Yi, Jeong Woo Kwak, Tae-Ho Hwang, Rae Woong Park, Seok Ho Kang
Journal: JAMA Network Open (2023)

Importance The antiandrogenic effect of the 5α-reductase inhibitor (5-ARI) has been investigated for its role in preventing male-predominant cancers. Although 5-ARI has been widely associated with prostate cancer, its association with urothelial bladder cancer (BC), another cancer experienced predominantly by males, has been less explored. Objective To assess the association between 5-ARI prescription prior to BC diagnosis and reduced risk of BC progression. Design, Setting, and Participants This cohort study analyzed patient claims data from the Korean National Health Insurance Service database. The nationwide cohort included all male patients with BC diagnosis in this database from January 1, 2008, to December 31, 2019. Propensity score matching was conducted to balance the covariates between 2 treatment groups: α-blocker only group and 5-ARI plus α-blocker group. Data were analyzed from April 2021 to March 2023. Exposure Newly dispensed prescriptions of 5-ARIs at least 12 months prior to cohort entry (BC diagnosis), with a minimum of 2 prescriptions filled. Main Outcomes and Measures The primary outcomes were the risks of bladder instillation and radical cystectomy, and the secondary outcome was all-cause mortality. To compare the risk of outcomes, the hazard ratio (HR) was estimated using a Cox proportional hazards regression model and difference in restricted mean survival time analysis. Results The study cohort initially included 22 845 males with BC. After propensity score matching, 5300 patients each were assigned to the α-blocker only group (mean [SD] age, 68.3 [8.8] years) and 5-ARI plus α-blocker group (mean [SD] age, 67.8 [8.6] years). Compared with the α-blocker only group, the 5-ARI plus α-blocker group had a lower risk of mortality (adjusted HR [AHR], 0.83; 95% CI, 0.75-0.91), bladder instillation (crude HR, 0.84; 95% CI, 0.77-0.92), and radical cystectomy (AHR, 0.74; 95% CI, 0.62-0.88). The differences in restricted mean survival time were 92.6 (95% CI, 25.7-159.4) days for all-cause mortality, 88.1 (95% CI, 25.2-150.9) days for bladder instillation, and 68.0 (95% CI, 31.6-104.3) days for radical cystectomy. The incidence rates per 1000 person-years were 85.59 (95% CI, 80.53-90.88) for bladder instillation and 19.57 (95% CI, 17.41-21.91) for radical cystectomy in the α-blocker only group and 66.43 (95% CI, 62.22-70.84) for bladder instillation and 13.56 (95% CI, 11.86-15.45) for radical cystectomy in the 5-ARI plus α-blocker group. Conclusions and relevance Results of this study suggest an association between prediagnostic prescription of 5-ARI and reduced risk of BC progression.
Human endogenous retrovirus onco-exaptation counters cancer cell senescence through calbindin
Authors: Jan Attig, Judith Pape, Laura Doglio, Anastasiya Kazachenka, Eleonora Ottina, George R. Young, Katey S.S. Enfield, Iker Valle Aramburu, Kevin W. Ng, Nikhil Faulkner, William Bolland, Venizelos Papayannopoulos, Charles Swanton, George Kassiotis
Journal: Journal of Clinical Investigation (2023)

Increased levels and diversity of human endogenous retrovirus (HERV) transcription characterizes most cancer types, linked with disease outcomes. However, the underlying processes are incompletely understood. We show that elevated transcription of HERVH proviruses predicts survival of lung squamous cell carcinoma (LUSC) and identify an isoform of CALB1, encoding Calbindin, ectopically driven by an upstream HERVH provirus under the control of KLF5, as the mediator of this effect. HERVH-CALB1 expression initiates in pre-invasive lesions and associates with their progression. Calbindin loss in LUSC cell lines impairs in vitro and in vivo growth and triggers senescence, consistent with a pro-tumor effect. However, Calbindin also directly controls the senescence-associated secretory phenotype (SASP), marked by secretion of CXCL8 and other neutrophil chemoattractants. In established carcinomas, CALB1-negative cancer cells become the dominant source of CXCL8, correlating with neutrophil infiltration and worse prognosis. Thus, HERVH-CALB1 expression in LUSC may display antagonistic pleiotropy, whereby the benefits of escaping senescence early during cancer initiation and clonal competition are offset by the prevention of SASP and pro-tumor inflammation at later stages.
Incremental prognostic value of biomarkers in <scp>PARADIGM‐HF</scp>
Authors: Kirsty McDowell, Ross Campbell, Joanne Simpson, Jonathan W. Cunningham, Akshay S. Desai, Pardeep S. Jhund, Martin P. Lefkowitz, Jean L. Rouleau, Karl Swedberg, Michael R. Zile, Scott D. Solomon, Milton Packer, John J.V. McMurray
Journal: European Journal of Heart Failure (2023)

It is uncertain how much candidate biomarkers improve risk prediction when added to comprehensive models including routinely collected clinical and laboratory variables in heart failure.Aldosterone, cystatin C, high-sensitivity troponin T (hs-TnT), galectin-3, growth differentiation factor-15 (GDF-15), kidney injury molecule-1, matrix metalloproteinase-2 and -9, soluble suppression of tumourigenicity-2, tissue inhibitor of metalloproteinase-1 (TIMP-1) and urinary albumin to creatinine ratio were measured in 1559 of PARADIGM-HF participants. We tested whether these biomarkers, individually or collectively, improved the performance of the PREDICT-HF prognostic model, which includes clinical, routine laboratory, and natriuretic peptide data, for the primary endpoint and cardiovascular and all-cause mortality. The mean age of participants was 67.3 ± 9.9 years, 1254 (80.4%) were men and 1103 (71%) were in New York Heart Association class II. During a mean follow-up of 30.7 months, 300 patients experienced the primary outcome and 197 died. Added individually, only four biomarkers were independently associated with all outcomes: hs-TnT, GDF-15, cystatin C and TIMP-1. When all biomarkers were added simultaneously to the PREDICT-HF models, only hs-TnT remained an independent predictor of all three endpoints. GDF-15 also remained predictive of the primary endpoint; TIMP-1 was the only other predictor of both cardiovascular and all-cause mortality. Individually or in combination, these biomarkers did not lead to significant improvements in discrimination or reclassification.None of the biomarkers studied individually or collectively led to a meaningful improvement in the prediction of outcomes over what is provided by clinical, routine laboratory, and natriuretic peptide variables.